Evaluation of standard and state of the art analytical technology-bioassays.

The development of biological assays for assessing potency is a critical component for monitoring the quality of therapeutic biologicals. Traditional cell-based bioassays, which are the most widely used, are typically based on a terminal cellular response such as cell proliferation or inhibition. While these assays can be very user-friendly, results often take days and sensitivity is sometimes not sufficient for the needs of the development programme. Recent improvements in analytical technology have led to new approaches in bioassay development. Many of these assays exploit cell signalling pathways far upstream from a terminal cellular response. Bioassays based on a cell signal are much more rapid, sensitive, and indicate stability better than their predecessors. Many of these newer assays are "hybrid" assays which combine the receptor signalling of traditional bioassays with the sensitivity of detection found in immunoassays. One such method, the Kinase Receptor Activation Assay (KIRA), works through the detection of receptor phosphorylation following analyte stimulation. Validations of newer technology assays, such as KIRA, require an individualized strategy due to their unique attributes. A thorough assessment of robustness should be paramount in the validation of these assays. Several examples of new technology platforms for bioassays are also discussed.